PDF(Pubmed)
Abstract：
Plasma membrane damage in vitrified oocytes is closely linked to mitochondrial dysfunction. However, the mechanism underlying mitochondria-regulated membrane stability is not elucidated. A growing body of evidence indicates that mitochondrial activity plays a pivotal role in cell adaptation. Since mitochondria work at a higher temperature than the constant external temperature of the cell, we hypothesize that suppressing mitochondrial activity would protect oocytes from extreme stimuli during vitrification. Here we show that metformin suppresses mitochondrial activity by reducing mitochondrial temperature. In addition, metformin affects the developmental potential of oocytes and improves the survival rate after vitrification. Transmission electron microscopy results show that mitochondrial abnormalities are markedly reduced in vitrified oocytes pretreated with metformin. Moreover, we find that metformin transiently inhibits mitochondrial activity. Interestingly, metformin pretreatment decreases cell membrane fluidity after vitrification. Furthermore, transcriptome results demonstrate that metformin pretreatment modulates the expression levels of genes involved in fatty acid elongation process, which is further verified by the increased long-chain saturated fatty acid contents in metformin-pretreated vitrified oocytes by lipidomic profile analysis. In summary, our study indicates that metformin alleviates cryoinjuries by reducing membrane fluidity via mitochondrial activity regulation.
摘要：
玻璃化卵母细胞的质膜损伤与线粒体功能障碍密切相关。然而,线粒体调节膜稳定性的潜在机制尚未阐明。越来越多的证据表明，线粒体活性在细胞适应中起着关键作用。由于线粒体在比细胞恒定外部温度更高的温度下工作，我们假设抑制线粒体活性可以保护卵母细胞在玻璃化过程中免受极端刺激.在这里，我们显示二甲双胍通过降低线粒体温度来抑制线粒体活性。此外,二甲双胍影响卵母细胞的发育潜能，提高玻璃化后的存活率。透射电子显微镜结果显示,在用二甲双胍预处理的玻璃化卵母细胞中,线粒体异常显著减少。此外，我们发现二甲双胍可短暂抑制线粒体活性。有趣的是,二甲双胍预处理降低玻璃化后细胞膜流动性。此外，转录组结果表明，二甲双胍预处理调节参与脂肪酸延伸过程的基因的表达水平，通过脂质组学分析，二甲双胍预处理的玻璃化卵母细胞中长链饱和脂肪酸含量的增加进一步证实了这一点。总之,我们的研究表明，二甲双胍通过线粒体活性调节降低膜流动性来减轻低温损伤。
